The role of insulin, glucagon and substrate availability in normal glucose homeostasis and in diabetes will be examined. The recently described evanescent effect of glucagon will be characterized by examining glucagon binding to liver receptors in glucagon treated animals. The relative responsiveness of the liver to other glycogenolytic hormones (e.g., epinephrine) in the face of refractoriness to glucagon will also be examined. In other studies the importance of altered binding of insulin to receptors on circulating monocytes in insulin resistance will be examined. Insulin binding to monocytes will be correlated with insulin action in intact man using the "insulin clamp" technique. In these studies obese subjects will be studied before and after 3 day-2 week fasts and after 1 week of re-feeding. In other studies the relative importance of insulin and glucagon in the pathogenesis of diabetes will be determined by examining the effects of somatostatin on fasting hyperglycemia and on glucose disposal and absorption in diabetic patients. BIBLIOGRAPHIC REFERENCES: Felig, P., and Sherwin, R. Carbohydrate homeostasis, the liver, and diabetes. In Progress in Liver Diseases, edited by H. Popper and F. Schaffner, Volume 5, Grune & Stratton, 1976. Felig, P. The metabolic events of starvation. Amer. J. Med., 60:117, 1976.